Elisa Nightingale

Covalent inhibition of deubiquitiases of Leishmania mexicana

About me

I completed a BSc in Biochemistry at the University of Leeds, which included an Industrial Placement Year in Global Clinical Trial Operations at MSD. I then worked at the cancer charity Yorkshire Cancer Research in the Research & Services team before beginning my PhD. My major interests in biochemistry, disease and development of novel therapeutics first attracted me to this project. I am excited to work in an area that has real-world impact. I am also looking forward to my 3-month placement at GSK, which will give me greater insight into the industrial side of science.

 

My project

My project focuses on Leishmania, a parasite responsible for the neglected tropical disease Leishmaniasis. Infection is spread by the bite of infected female sandflies, and the disease is prevalent across many parts of the globe. Unfortunately safe and effective treatments for leishmaniasis are lacking.

Previous research has indicated that certain deubiquitinase (DUB) enzymes of Leishmania mexicana are essential for parasite survival, suggesting a strategy to prevent/treat infection. To investigate this, this project will cover four aims. First, a screen of a covalent fragment library against selected DUB proteins will be performed at GSK to identify potential inhibitors. This will be followed by the crystallisation of DUB-inhibitor complexes to aid the development of higher potency inhibitors. Finally, on-target engagement of the inhibitor in L. mexicana cells will be measured, and the downstream biological effects of DUB inhibition will be investigated. 

Connect

LinkedIn: https://www.linkedin.com/in/elisa-nightingale/